NEURO-ONCOLOGY PROGRAM PROJECT SUMMARY The primary goals of the Mayo Clinic Cancer Center (MCCC) Neuro-Oncology (NONC) Program are to identify underpinning pathogenic mechanisms of brain tumor biology and to develop interventions that result in improved duration and quality of life for patients with brain cancer. To achieve this goal, work within the Program can be divided into 3 Specific Aims. 1) Brain Tumor Biology where investigations will define basic mechanisms of brain tumor biology and unique tumor vulnerabilities that can be exploited in the other 2 Aims; 2) Biomarkers that can be used in clinical practice to provide patients and physicians with greater understanding of prognosis and to guide optimal, personalized therapeutic interventions for brain tumors; 3) Novel Therapeutic Strategies to improve response and survival duration, reduce disease symptoms, and improve quality of life of patients with brain tumors. Notable accomplishments of the Program in the last funding period include a) seminal contributions towards the discovery of genetic loci associated with brain tumorigenesis; b) development and characterization of FDOPA PET imaging as an improved targeting strategy for surgical and radiotherapy planning for gliomas; c) use of patient-derived xenograft (PDX) models to define predictive biomarkers for response to combination therapies; d) continued integrated genomic, transcriptomic and proteomic analyses of patient derived xenografts and glioma stem-like cell cultures (GSCs) as an institutional and national resource. Drs. Jann Sarkaria (Mayo Clinic in Rochester), Joseph Loftus (Mayo Clinic in Arizona), and Steven Rosenfeld (Mayo Clinic in Florida) provide leadership of the Program. They receive input from the NONC Executive Committee whose membership spans all 3 MCCC sites and encompasses diverse scientific expertise in neuro-pathology, neuro-oncology, tumor biology, neurosurgery, radiation oncology, neuro-radiology and biostatistics. The Program makes extensive use of CCSG-supported Shared Resources, particularly Biospecimens Accessioning and Processing, Pathology Research, Bioinformatics, Biostatistics, Pharmacology, Survey Research, and the Clinical Research Office. The Program capitalizes on Mayo's strengths in neurosurgery, epidemiology, molecular biology, neuropathology, and imaging, and integrates them with Mayo Clinic's extensive clinical and clinical trial experience in treatment of primary brain tumors. The Program comprises 24 Primary, 4 Secondary, and 10 Associate members from 14 Departments across all 3 sites. The Program is anchored by 14 of the Primary members with R01 or equivalent peer- reviewed funding. Recruitment in the current funding period has significantly bolstered the breadth of the Program across all 3 sites. Total direct grant funding within the Program is $4.9M, with $2.9M in peer reviewed funding (79% from NCI). In the past 5 years, the Program has generated 344 publications, 35% of which are intraprogrammatic collaborations, and 18% interprogrammatic collaborations.